rs1053320

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001848.3(COL6A1):c.2796C>T(p.Ser932Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,612,542 control chromosomes in the GnomAD database, including 68,834 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 7820 hom., cov: 35)

Exomes 𝑓: 0.29 ( 61014 hom. )

Consequence

COL6A1
NM_001848.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -4.25

Publications

21 publications found

Variant links:

Genes affected

COL6A1 (HGNC:2211): (collagen type VI alpha 1 chain) The collagens are a superfamily of proteins that play a role in maintaining the integrity of various tissues. Collagens are extracellular matrix proteins and have a triple-helical domain as their common structural element. Collagen VI is a major structural component of microfibrils. The basic structural unit of collagen VI is a heterotrimer of the alpha1(VI), alpha2(VI), and alpha3(VI) chains. The alpha2(VI) and alpha3(VI) chains are encoded by the COL6A2 and COL6A3 genes, respectively. The protein encoded by this gene is the alpha 1 subunit of type VI collagen (alpha1(VI) chain). Mutations in the genes that code for the collagen VI subunits result in the autosomal dominant disorder, Bethlem myopathy. [provided by RefSeq, Jul 2008]

COL6A1 Gene-Disease associations (from GenCC):

Bethlem myopathy 1A
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P
collagen 6-related myopathy
Inheritance: SD, AD, AR Classification: DEFINITIVE Submitted by: ClinGen
Ullrich congenital muscular dystrophy 1A
Inheritance: AD, AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Bethlem myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ullrich congenital muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

COL6A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 21-46003722-C-T is Benign according to our data. Variant chr21-46003722-C-T is described in ClinVar as Benign. ClinVar VariationId is 93870.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001848.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COL6A1	NM_001848.3	MANE Select	c.2796C>T	p.Ser932Ser	synonymous	Exon 35 of 35	NP_001839.2	P12109

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
COL6A1	ENST00000361866.8	TSL:1 MANE Select	c.2796C>T	p.Ser932Ser	synonymous	Exon 35 of 35	ENSP00000355180.3	P12109
COL6A1	ENST00000498614.5	TSL:1	n.1030C>T		non_coding_transcript_exon	Exon 6 of 6
COL6A1	ENST00000866134.1		c.1110C>T	p.Ser370Ser	synonymous	Exon 7 of 7	ENSP00000536193.1

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47410

AN:

152144

Hom.:

7813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.410

Gnomad AMI

AF:

0.167

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.220

Gnomad EAS

AF:

0.159

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.251

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.283

GnomAD2 exomes

AF:

0.267

AC:

66141

AN:

247462

AF XY:

0.261

show subpopulations

Gnomad AFR exome

AF:

0.406

Gnomad AMR exome

AF:

0.287

Gnomad ASJ exome

AF:

0.218

Gnomad EAS exome

AF:

0.147

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.255

GnomAD4 exome

AF:

0.286

AC:

417096

AN:

1460280

Hom.:

61014

Cov.:

AF XY:

0.282

AC XY:

204625

AN XY:

726430

show subpopulations

African (AFR)

AF:

0.414

AC:

13844

AN:

33474

American (AMR)

AF:

0.286

AC:

12767

AN:

44632

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

5736

AN:

26110

East Asian (EAS)

AF:

0.182

AC:

7234

AN:

39688

South Asian (SAS)

AF:

0.206

AC:

17802

AN:

86240

European-Finnish (FIN)

AF:

0.250

AC:

13109

AN:

52354

Middle Eastern (MID)

AF:

0.214

AC:

1237

AN:

5768

European-Non Finnish (NFE)

AF:

0.296

AC:

329225

AN:

1111654

Other (OTH)

AF:

0.267

AC:

16142

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

21437

42873

64310

85746

107183

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10890

21780

32670

43560

54450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.312

AC:

47448

AN:

152262

Hom.:

7820

Cov.:

AF XY:

0.309

AC XY:

22999

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.409

AC:

17012

AN:

41562

American (AMR)

AF:

0.313

AC:

4789

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.220

AC:

765

AN:

3472

East Asian (EAS)

AF:

0.160

AC:

826

AN:

5176

South Asian (SAS)

AF:

0.196

AC:

947

AN:

4828

European-Finnish (FIN)

AF:

0.251

AC:

2664

AN:

10602

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19644

AN:

67998

Other (OTH)

AF:

0.280

AC:

592

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1763

3526

5290

7053

8816

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

460

920

1380

1840

2300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.297

Hom.:

4713

Bravo

AF:

0.321

Asia WGS

AF:

0.176

AC:

617

AN:

3478

EpiCase

AF:

0.281

EpiControl

AF:

0.278

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Bethlem myopathy 1A (2)

Collagen 6-related myopathy (1)

not provided (1)

Ullrich congenital muscular dystrophy 1A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.038

(source)

DANN

Benign

0.73

PhyloP100

-4.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over